Regio- and stereoselective 1(S)-camphorsulfonylation of monoalkoxycalix[4]arenes V.I. Boyko a , A.V. Yakovenko a , Yu.I. Matvieiev a , O.I. Kalchenko a , O.V. Shishkin b , S.V. Shishkina b , V.I. Kalchenko a, * a Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Murmanska Street 5, 02660, Kyiv-94, Ukraine b Institute for Single Crystals, National Academy of Sciences of Ukraine, Lenin Avenue 60, Kharkiv 61001, Ukraine article info Article history: Received 5 February 2008 Received in revised form 6 May 2008 Accepted 22 May 2008 Available online 27 May 2008 Keywords: Alkoxycalix[4]arenes 1(S)-Camphorsulfonylation Heterosubstituted calixarenes Diastereomers abstract The reaction of calix[4]arene monoalkyl ethers with 1(S)-camphor-10-sulfonyl chloride yields 1,2- or 1,3- alkoxy-1(S)-camphorsulfonyloxycalixarenes depending on the nature of the base used. In the presence of triethylamine only 1,3-substituted derivatives are formed. Two diastereomers of the 1,2-substituted calixarenes with clockwise and anticlockwise arrangement of alkyl and camphorsulfonyl groups at the narrow rim are formed in the presence of sodium hydride or potassium carbonate. Due to chiral in- duction of the camphorsulfonyl group the 1,2-substitution is diastereoselective. The ratio of dia- stereomers formed is dependent on the alkyl groups at the calixarene narrow rim. Ó 2008 Published by Elsevier Ltd. 1. Introduction The design of highly selective artificial receptors based on cal- ixarenes is an intensively developed area of supramolecular chemistry. 1,2 Calix[4]arenes due to their unique cap-shaped archi- tecture and their ability to be functionalized in various ways have been used as building blocks for the construction of a large variety of host molecules with different supramolecular functions. Utili- zation of calixarenes as chemical sensors, extractants for nuclear waste treatment, materials for non-linear optics and bio-active compounds has been reported. 1,3,4 Functionalization of phenolic hydroxy groups at the narrow (lower) rim of calix[4]arenes is a relevant stage in the design of such materials. In spite of numerous efficient methods for chemical modifica- tion of calixarenes, the regio- and stereoselective introduction of functional groups, however, continues to be a challenge to the synthetic chemist. The regioselective substitution of calix[4]arenes at the narrow rim is mainly due to the different acidities of the phenolic OH groups, which can be selectively ionized by using an appropriate base. 5 While distal 1,3-di(hetero)functionalization may be considered as one of the standard reactions in calix[4]arene chemistry, 6–9 only a few examples of proximal 1,2-di(hetero)- functionalization are known. All these compounds were obtained by multistep synthesis involving a protection–deprotection se- quence 6,10,11 or rearrangements. 12–15 The methods for synthesis of 1,2-heterofunctionalized calix[4]arenes attract considerable in- terest as the shortest way to inherently chiral calixarenes of the ABHH type, the chirality of which originates from the asymmetric array of achiral residues on the calixarene skeleton. 2. Results and discussion In this paper, we investigate regio- and stereoselective reactions of monoalkoxycalixarenes with 1(S)-(þ)-camphor-10-sulfonyl chloride. Sulfonylation of monoalkoxycalixarenes 1a–c by 1.1 mol of 1(S)-camphorsulfonyl chloride with an excess of triethylamine (Scheme 1) in toluene is regioselective and gives exclusively 1,3- monoalkoxysulfonyloxycalixarenes 2a–c in the cone conformation. The observed selectivity can be explained by the different acidities of the phenolic OH groups. The OH group in the distal position to the alkylated phenol moiety of monoalkoxycalixarenes 1 is more acidic than that in the proximal position. In the presence of a weak base (triethylamine) the reaction proceeds, seemingly, through the intermediate monoanion A, which is stabilized by two OH/O hy- drogen bonds. 5 The substitution pattern at the narrow rim of cone shaped cal- ixarenes 2a–c is proved by 1 H NMR spectra. All axial and equatorial protons of methylene bridges are diastereotopic. The signals of the axial protons reveal as three doublets at 4.0–4.5 ppm. The AB doublets for the equatorial protons of the methylene bridges * Corresponding author. Tel.: þ38 044 559 06 67; fax: þ38 044 573 26 43. E-mail address: vik@ioch.kiev.ua (V.I. Kalchenko). Contents lists available at ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet 0040-4020/$ – see front matter Ó 2008 Published by Elsevier Ltd. doi:10.1016/j.tet.2008.05.106 Tetrahedron 64 (2008) 7567–7573